ERI: Degradation of Polyelectrolyte Complexes via Enzyme Addition

Lehigh University, Bethlehem PA

Investigators

Abstract

Advanced treatments for cancer, HIV, and other diseases have begun incorporating multi-drug therapeutics to provide better care for patients. When using multi-drug therapeutics, it is challenging, yet necessary, to administer multiple drugs during a session to achieve the full therapeutic effect. A solution to this challenge is to deliver both drugs at the same time. One downside, however, is the need for each drug to be deposited or reach a separate part of the body with different types of release kinetics. The overarching goal of this ERI project is to investigate the use of charged polymer complexes as a novel platform for dual drug delivery with the ability to regulate the release profiles of these drugs independently of each other. To advance this goal, the Principal Investigator aims to investigate two avenues: (1) the degradation of solid polymer complexes after enzyme introduction and (2) the degradation of liquid polymer complexes that break down after adding an appropriate enzyme. The successful completion of this project will benefit society by laying the groundwork for dual drug delivery systems and advancing national health and welfare. Graduate and undergraduate student education, mentoring, and training will further the societal benefits of this project. Although groups have investigated polyelectrolyte complexation and degradable polymers, there has not been significant investigation of integrating these two concepts together. This ERI project will address this gap by complexing an enzymatically degradable carboxymethyl cellulose (CMC) polymer with an oppositely charged polyelectrolyte, such as poly(L-lysine). This research is the first step toward developing a system where the Principal Investigator can utilize the electrostatic nature of polyelectrolyte complexes, trigger drug release, and dismantle these complexes through the enzymatic degradation of CMC. The PI seeks to use both liquid-liquid and solid-liquid phase separation as starting points for evaluating polymer complex degradation. The three objectives of this ERI project are: (1) investigating the ability to complex a charged degradable polymer with an oppositely charged peptide or protein; (2) monitoring the kinetics of how the degradable polymer breaks down both as part of the complex and free in solution; and (3) through the incorporation of a third charged species to act as a model drug and monitor the release kinetics of the drug. After conducting fundamental studies using absorbance studies, brightfield microscopy, and enzyme assays, future research can further design systems for dual drug delivery with two different release mechanisms - release via changes in electrostatics and polymer degradation. The successful completion of this project has the potential for transformative impact through the generation of a dual drug delivery platform with tunable, independent release kinetics while furthering a fundamental understanding of phase separation and polymer degradation. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.